Pupillary Reaction to Opioids on Awake Subjects: A Systematic Review

To evaluate the correlation between opioid administration, pupillary changes measured by pupillometry, and patient-reported pain levels in nonprocedural settings, and to assess the utility of pupillometry as an objective tool for pain assessment and opioid efficacy.

Systematic review of published literature.

A literature search was conducted in February 2022 using PubMed, CINAHL, Web of Science, and EMBASE to identify studies examining the relationship between opioids, pupillary responses, and pain.

A total of 160 articles were screened, and 14 studies met inclusion criteria for final analysis. Studies were evaluated for associations between opioid administration, pupillary measurements, and pain levels, as well as for reported confounding factors influencing pupillary response.

Most studies demonstrated a significant association between opioid administration and pupillary constriction or altered pupillary reflexes. Several studies also identified correlations between pupillary responses and reported pain levels. Age, intraoperative medications, and individual physiological variability were found to influence pupillary measurements and may act as confounders.

Pupillometry shows promise as an objective indicator of opioid effect and pain response, particularly in settings where subjective pain reporting may be limited or unreliable. However, its interpretation must account for patient-specific and clinical confounding factors.

Pupillary measurement may serve as a useful adjunct to traditional pain assessment tools in outpatient and postoperative settings. Incorporating pupillometry alongside routine vital signs-such as blood pressure, respiratory rate, and temperature-may enhance pain evaluation and support safer opioid prescribing and monitoring practices. Further research is needed to guide clinical implementation and establish standardized protocols.